Research Article: The effects of graded caloric restriction: XII. Comparison of mouse to human impact on cellular senescence in the colon

Date Published: March 25, 2018

Publisher: John Wiley and Sons Inc.

Author(s): Luigi Fontana, Sharon E. Mitchell, Boshi Wang, Valeria Tosti, Thijmen van Vliet, Nicola Veronese, Beatrice Bertozzi, Dayna S. Early, Parcival Maissan, John R. Speakman, Marco Demaria.


Calorie restriction (CR) is an effective strategy to delay the onset and progression of aging phenotypes in a variety of organisms. Several molecular players are involved in the anti‐aging effects of CR, but mechanisms of regulation are poorly understood. Cellular senescence—a cellular state of irreversible growth arrest—is considered a basic mechanism of aging. Senescent cells accumulate with age and promote a number of age‐related pathologies. Whether environmental conditions such as diet affect the accumulation of cellular senescence with age is still unclear. Here, we show that a number of classical transcriptomic markers of senescent cells are reduced in adult but relatively young mice under CR. Moreover, we demonstrate that such senescence markers are not induced in the colon of middle‐age human volunteers under CR in comparison with age‐matched volunteers consuming normal Western diets. Our data support the idea that the improvement in health span observed in different organisms under CR might be partly due to a reduction in the number of senescent cells.

Partial Text

Human lifespan and health span have risen significantly in recent decades (Vaupel, 2010). Yet, aging is a progressive and generalized deterioration of the functional capacities of an organism which strongly contributes to tissue failure. Accordingly, age is one of the largest single risk factors for developing diseases, from neurodegeneration to cancer. The effects of aging are largely influenced by genetic and environmental conditions. While genetic manipulations of model organisms have set important milestones for the understanding of the aging process, calorie restriction (CR) is a well‐established nongenetic approach able to improve health span and lifespan in different organisms (Finkel, 2015). However, the precise mechanisms by which CR improves health are not fully understood (Speakman & Mitchell, 2011; Fontana & Partridge, 2015).

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